Phalloplasty Complicated by Penile Artery Thrombosis, Recurrent Extended-Spectrum Beta-Lactamase (ESBL) Urinary Tract Infection (UTI), Colovesical Fistula, and Enterococcus Faecalis Endocarditis.

Enterococcus faecalis is an enteric microorganism that, if introduced into the vasculature, is an uncommon cause of infective endocarditis. Timely diagnosis, appropriate treatment measures, and close follow-up are key to therapeutic success. Antibiotic therapy is the mainstay of therapy, and surgical intervention is sometimes indicated. Here we present a novel case of a 45-year-old transgender male with Factor V Leiden deficiency who was found to have Enterococcus faecalis mitral valve endocarditis due to the postoperative complications of colovesical fistula formation leading to extended-spectrum beta-lactamase (ESBL) urinary tract infection (UTI) and E. faecalis bacteremia in the setting of recent phalloplasty, mastectomy, and vaginal eversion.

Effects of subchronic acrylamide treatment on the endocrine pancreas of juvenile male Wistar rats.

Acrylamide (AA) is a well-known industrial monomer with carcinogenic, mutagenic, neurotoxic and endocrine disruptive effects on living organisms. AA has been the subject of renewed interest owing to its presence in various food products. We investigated the potential adverse effects of oral AA treatment on the endocrine pancreas of juvenile rats using histochemical, immunohistochemical, stereological and biochemical methods. Thirty juvenile male Wistar rats were divided into one control and two AA treatment groups: one treated with 25 mg/kg AA and the other treated with 50 mg/kg AA for 21 days. We found a significant decrease in ß-cell mass. The significant decrease in ß-cell optical density and unchanged blood glucose levels indicate that normoglycemia in AA treated rats may result from intensive exocytosis of insulin-containing secretory granules. By contrast with ß-cells, we observed increased α-cell mass. The slight increase in α-cell cytoplasmic volume suggests retention of glucagon in α-cells, which is consistent with the significant increase in α-cell optical density for AA treated animals. The number of islets of Langerhans did not change significantly in AA treated groups. Our findings suggest that AA treatment causes decreased ß-cell mass and moderate α-cell mass increase in the islets of Langerhans of juvenile male Wistar rats.

Antiradical activity of catecholamines and metabolites of dopamine: theoretical and experimental study.

The importance of molecules with antiradical potency that are produced in the human body has significantly increased. Among others, neurotransmitters and their metabolites act as the first line of defense against oxidative stress in the peripheral endocrine and the central nervous systems. Dopamine (DO), epinephrine (EP), norepinephrine (NE), l-DOPA, catechol, and three metabolites of dopamine (3-methoxytyramine (3-MT), homovanillic acid (HO), and 3,4-dihydrophenylacetic acid (DOPAC)) were investigated for their antiradical potency via computational methods and DPPH assay. Density functional theory calculations were used to determine the most probable reaction mechanism based on the thermodynamic parameters. These results suggested that hydrogen atom transfer (HAT)/proton-coupled electron transfer (PCET) and sequential proton loss electron transfer (SPLET) mechanisms are preferable in polar solvents. Several techniques were employed to differentiate between HAT and PCET mechanisms via examination of the transition state structures. Kinetic studies of HAT/PCET and electron transfer (ET) reactions, the second step of SPLET, have proven that ET is much faster for an order of 105-106. Based on this, it was concluded that SPLET was the dominant mechanism for the antiradical activity towards DPPH radicals in polar solvents. The findings suggest that all the investigated molecules can be classified as excellent antiradical scavengers, except for 3-MT and homovanillic acid.

Assessment of preschool psychopathology in Serbia.

The utility of the Child Behavior Checklist for Ages 1.5-5 (CBCL/1.5-5) and the Caregiver-Teacher Report Form (C-TRF) to the Serbian children is largely unknown and has not been studied. An aim of this study was to examine rates and distribution of emotional and behavioral problems among 4 to 6-year-old children in the Serbia. Country differences between our Serbian sample and the original U.S. sample, gender differences, and cross-informant agreement between teachers and parents were also to be examined. The CBCL/1.5-5 and the C-TRF was completed by parents and teachers respectively on 512 preschoolers in the city of Novi Sad, Serbia. Internal consistency of the scales was analyzed using Cronbach alpha (α). The comparison of behavioral/emotional syndromes raw scores was performed by t test. CBCL/1.5-5 prevalence rate of the Total Problems score in the clinical range was 13.4%, while the C-TRF prevalence rate for girls was 9.8% and for boys 8.8%. Our findings revealed that parent reported more problems than teachers on almost all scales across gender with the mean cross-informant correlation of 0.24. This study documents gender differences, with boys scoring significantly higher than girls on all externalizing related problem scales on both questionnaires, but with no gender differences on internalizing problems on either questionnaire. Results support the applicability of the Serbian version of the CBCL/1.5-5 and C-TRF and can be recommended for use in clinical and research settings.

Vitamin C Depletion in Prenatal Guinea Pigs as a Model of Lissencephaly Type II.

Humans and guinea pigs are unable to produce vitamin C, with deficiency resulting in a well-known disorder of collagen synthesis. Pial basement membrane structure preservation is essential in the proper migration of neurons. In our study, intrauterine deprivation of vitamin C in guinea pig fetuses led to a collagen synthesis disorder, weakness, and finally a breach of pial basement membrane. We found excessive migration of the external germinal layer cells into the subarachnoid space of the cerebellum through defects in the pial basement membrane. The changes ranged from focal rupture of pial basement membranes to their complete disintegration. The loss of proper folia formation resulted in macroscopically visible flattening of the cerebellar surface. Different grades of dysplastic changes in the folia of the cerebellar cortex were observed in 2 experimental groups assigned different limits to mark the time of commencement and duration of vitamin C deprivation. The most severe form of dysplastic changes was characterized by marked irregularity of the cerebellar cortex similar to that in lissencephaly type II. Thus, prenatal vitamin C deficiency represents a novel animal model to study the effects of collagen synthesis on development of breaches in the pial basement membrane, disordered migration of neurons, dysplasia of cerebellar cortex, and the pathogenesis of lissencephaly.

Parent-reported behavioural and emotional problems in Albanian Kosovar children.

AIMS: Because no epidemiological study has been conducted of children's mental health problems in Kosova, which experienced a traumatic war in 1998-99, we conducted the first national epidemiological survey of children's mental health ever undertaken in Kosova. METHODS: Participants were 1374 Kosovar children ages 6-18 recruited through schools (60% from urban areas). Parent-reported behavioural and emotional problems were assessed using the Child Behaviour Checklist (CBCL/6-18). Kosovar findings were compared with findings from five other Central and Eastern European societies (Poland, Romania, Lithuania, Serbia and Croatia), plus the US. RESULTS: Confirmatory factor analysis (CFA) indicated that the CBCL 8-syndrome model manifested good fit to the Kosovar data. Mean item ratings and Cronbach's alphas were very similar to those of the other six societies. Kosova's mean Total Problems score fell in the middle of the range of the seven societies compared. CBCL scores were higher for adolescents (12-18), urban children, and those whose parents had limited education compared with younger (6-11), rural, and more socially advantaged children. CONCLUSIONS: Strong consistency was found between Kosovar findings and those for neighbouring countries with respect to CFA results, mean item ratings, alphas and problem score levels. Results of this epidemiological survey highlight the utility of the CBCL for identifying Kosovar Albanian children with mental health service needs.

Diagnosis and Treatment of Venous Malformations. Consensus Document of the International Union of Phlebology (IUP): updated 2013.

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects) . These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/ persistence rates, high morbidity following non-specific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular sub-types of VMs. This incorporated the embryological ongm, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustrated as a separate topic to differentiate from isolated VMs and to rectify the existing confusion with name-based eponyms such as Klippei-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndromebased VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Guideline. Diagnosis and treatment of venous malformations. consensus document of the international union of phlebology (iup): updated-2013.

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects). These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/persistence rates, high morbidity following nonspecific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular subtypes of VMs. This incorporated the embryological origin, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustratedas a separate topic to differentiate from isolated VMs and to rectify the existing confusion with namebased eponyms such as Klippel-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndrome-based VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Concordant response to pharmacotherapy in monozygotic twins with schizoaffective disorder.

BACKGROUND: Schizoaffective disorder (SAD) represents one of the most confusing and controversial concepts in psychiatry. Prevalence is less than 1%, but despite that it has a major influence on an individual and community. There is an increased risk for schizophrenia and mood diorders in first degree relatives with SAD, according to DSM IV. This paper describes the concordant clinical response of a pair of monozygotic twins with SAD when treated with risperidon and valproic acid. We found that their clinical symptoms were very similar and both brothers expressed hipomanic and depressive episode prior to full onset of SAD-psychotic symptoms with correlations of elevated mood, and first psychiatric hospitalization at the age of 19 (patient A) and 18 (patient B). Their response to the combined treatment with risperidon and valproic acid has been also similar both in intensity and in the pattern of symptoms that have improved.

Contribution of immunohistochemistry in the differential diagnosis of non-small cell lung carcinomas on small biopsy samples.

PURPOSE: Targeted therapy increases survival and the quality of life of non-small cell lung cancer (NSCLC) patients but it needs precise histological subtyping. The present study evaluated 6 monoclonal antibodies for the differential diagnosis of NSCLC on small-sized tissue samples. METHODS: 50 small-sized tissue samples were obtained by bronchoscopy or fine needle aspiration biopsy (FNAB). According to morphology before immunohistochemistry 2 squamous cell carcinomas (SCC), 6 adenocarcinomas (AC), 9 NSCLC-probably SCC, 11 NSCLC-probably AC and 22 unclassified NSCLCs were diagnosed. Thyroid transcription factor-1 (TTF-1), cytokeratin 5/6, cytokeratin 7, p63, and the neuroendocrine markers CD56 and synaptophysin were used in the differential diagnosis of NSCLC. RESULTS: After immunohistochemistry 13 (26.0%) SCC, 27 (54.0%) AC, 3 (6.0%) NSCLC with neuroendocrine differentiation (NSCLC-NE) and 7 (14.0%) NSCLC- unclassified were diagnosed. Twenty-two NSCLC- unclassified were further diagnosed as SCC (n=7), AC (n=7) NSCLC-NE (n=2) and 6 remained NSCLC- unclassified. Significant difference was found between definitely diagnosed 8 NSCLCs and 15 ACs (20.5 vs. 38.57percnt;, p=0.008). TTF-1 and cytokeratin 7 were expressed in 85.2% (23/27) of AC, and cytokeratin 5/6 and p63 in 100% (13/13) of SCC. Positivity of CD56 and synaptophysin in 3 NSCLC determined NSCLC-NE. CONCLUSION: No one monoclonal antibody is totally specified for one histological type of tumor and its origin. Combination of TTF-1, cytokeratin 7, p63, cytokeratin 5/6, CD56 and synaptophysin allows for differentiation of NSCLC but Napsin-A for AC differentiation and chromogranin A for NSCLC-NE differentiation should be added in an optimal panel.

Some psychological characteristics of adolescents hospitalized following a suicide attempt.

BACKGROUND: In most countries, suicide is second or third leading cause of death in youth. Suicidal tendencies among youth have been the subject of extensive research. Reports of increased rate of suicide attempts in the past few decades indicate that this phenomenon has not been fully understood. AIM: The aim of this study was to better understand the phenomenon of adolescent suicide behavior by defining some specific psychological characteristics of adolescents who were hospitalized at the psychiatric ward because of the suicide attempt. METHODS: 62 participants were assigned to two groups: clinical (adolescents who were hospitalized after a suicide attempt) and non-clinical (adolescents without psychiatric symptoms). They filled in a series of instruments: a questionnaire examining adolescents' demographic characteristics, Rosenberg's Self-Esteem Scale, Youth Self Report. RESULTS: Compared to the non-clinical populaton adolescents attempting suicide had significantly more frequent suicidal thoughts (χ2 = 18.627, df = 1, p < .01), higher incidence of earlier attempts (χ2 = 10.008, df = 1, p < .01), they abused substances more often (χ2 = 7.398, df=1, p < .01), had higher incidence of fathers' psychopathology (χ2 = 11.77, df = 1, p < .01), lower level of self-esteem (t = 4.23, p < .01), and more significant expression of internalized (F/1.60/ = 19.02; p < .01) as well as externalized problems (F/1.60/ = 4.41; p < .05). CONCLUSIONS: This study point to some of the characteristics of adolescents who were hospitalized after a suicide attempt.  

Role of sexual abuse in development of conversion disorder: case report.

Described case report speaks in favour of the relation between childhood sexual abuse with the development of conversion disorder. Following Salmonella poisoning, adolescent, at the age of 16, develops series of severe somatic symptoms. Results of diagnostic procedures excluded organic foundation of the symptoms; diagnosis of conversion disorder is established. Soon, patient's problems stop abruptly and spontaneously, and the aetiology of the mental disorder remains unexplained. Six years later, adolescent reveals for the first time data about the childhood sexual abuse during the forensic evaluation (within the court process related to the request for compensation for the complications which occurred following the Salmonella infection). During the forensic evaluation, we had insight into the previous medical history, while an interview, psychological and psychiatric exploration was conducted with the examinee. Data about the sexual abuse retrospectively explain the dynamics of the development of conversion disorder. The described case indicates that sexual abuse of children and adolescents frequently remains unrecognized, which has sequels for treatment and prevention of subsequent consequences for mental health. It is important to emphasize the significance of examining history of abuse during the diagnostic of certain mental disorders. Forensic implications of the case have not been discussed in details for the needs of this report.

Clozapine-induced pericarditis.

OBJECTIVE: To report a case of a patient treated with clozapine who developed pericarditis with pericardial effusion that resolved when the drug was discontinued. METHOD: Case report of a 21-year-old man with psychotic disorder that had been stable on clozapine therapy for five months (after failure of atypical antipsyhotic agents) presented to the emergency department complaining of chest pain and progressive shortness of breath that had lasted for a few days. Echocardiography showed a pericardial effusion suggestive of a cardiac tamponade, and the fluid was removed by pericardiocentesis. All other possible causes of the pericardial effusion were ruled out and clozapine was suspected as the most likely explanation. Clozapine was discontinued and the patient's symptoms improved markedly. DISCUSSION: According to the Naranjo probability scale, clozapine is a probable cause of pericarditis. Although clozapine is a known cause of myocarditis and cardiomyopathy, there are only several reports in the literature describing clozapine-induced pericarditis and pericardial effusion. In our patient, the pericardial effusion cleared within several days following clozapine discontinuation. CONCLUSION: There have been only a few cases of clozapine-induced pericarditis reported in the literature, however this adverse effect of clozapine can occur, as this case report clearly demonstrates. Cardiac adverse effects of clozapine are potentially life threatening, hence early recognition is essential to prevent serious outcomes.

The impact of heroin on visual memory.

INTRODUCTION AND AIM: Heroin abuse can lead to organic damage of cerebral structures, including sequels in cognitive and affective sphere, which are in positive relation with the duration of substance usage. Memory is one of the cognitive functions which is highly sensitive to opiate toxic effects. The aim of this research was determination of heroin impact on the visual memory of addicts, as well as the existence of specific relation of potential deficiencies in visual memory with the duration of substance use. METHODS: The research included 90 examinees, divided into three groups, depending on the duration of heroin intake. We used questionnaire for basic socio-demographic and addictological traits of examinees; Wechsler's scale for the assessment of the intelligence and Visual Memory Test (TVP), for the assessment of the visual memory. RESULTS: The achievements of heroin addicts with different duration of the substance abuse differ significantly (F = 1.83; df = 12; p < 0.05). Total number of errors examinees make in the first series of TVP (immediate visual memory) grows, almost linearly in the function of the duration of heroin abuse (p < 0.05), but in neither of groups meets criteria for the visual memory impairment. Deficiency of the delayed visual memory occurs in examinees who use heroin for one (total number of errors = 6.46; participation of typical organic errors = 31.7%) and longer than five years (total number of errors = 7.66; participation of typical organic errors = 26.7%). Univariate covariance analysis separates the average daily dosage of heroin as the most significant variable that contributes to the expression of the aforementioned deficiencies (F = 4.21; df = 2; p < 0.05). CONCLUSION: Heroin abuse leads to damage of delayed visual memory, whereby for the observed effect intake of the substance for a period longer than one year is necessary.

Gender and age trends of histological types of lung cancer in a 20-year period: pathological perspective.

PURPOSE: To find out the trends of distribution in different histological types of lung cancer in both genders in a period of 20 years. METHODS: The most frequent histological types of lung cancer in tissue specimens obtained by bronchoscopy or percutaneous needle biopsy were analysed in terms of age and gender. The studied population included 6289 patients (16.6% females and 83.1% males). Statistical significance was established by x(2) test at the level p<0.05. RESULTS: Squamous cell carcinoma (SCC) prevailed in the total number of patients in all investigated years (58.0%), and separately in male (60.4%) and female (45.7%) patients. This histological type was predominant in all age groups in both genders (41.6% in males and 38.1% in females). CONCLUSION: SCC has the highest incidence in Serbia. Continuous campaign against smoking and helping its cessation, improving working and socioeconomic conditions is a strategy for decreasing all histological types of lung cancer patients.

Prediction and biochemical characterization of intrinsic disorder in the structure of proteolysis-inducing factor/dermcidin.

Proteolysis-inducing factor/dermcidin (PIF/DCD) is a novel human gene, located on chromosome 12, locus 12q13.1, that encodes a secreted 110-amino acid protein. Two transcripts for the protein have been identified in normal skin, breast, placenta and brain, and in various primary and metastatic tumor cells. The putative native-state structure of PIF/DCD has not been resolved. Here, we describe some biochemical features of the soluble recombinant 11-kDa protein produced in Escherichia coli. The native 11-kDa polypeptide displayed an anomalous mobility on 1% SDS-PAGE under reduced conditions and appeared as a single approximately 16-kDa band. Under nonreduced conditions, we detected by mass spectrometry, the presence of multiple peaks corresponding to m/z values of 21 kDa, which we confirmed as a dimeric form with a disulfide bridge between cysteine 34 of each 11-kDa monomer. The native protein exhibited an unusually high susceptibility to proteolytic attack by trypsin, and up to 13 peptides derived from its C-terminus were produced after 5 min of incubation. The secondary structure analysis of PIF/DCD native protein in aqueous solution, by circular dichroism spectroscopy, revealed regions with non-well-defined secondary structure but that acquired alpha-helix and beta-sheet secondary structures in the presence of TFE/water mixtures and micellar and non-micellar SDS molecules. By using PONDR, DisEMBL, DisProt, and GlobPlot computational predictors, we identified a long disorder region at the N-terminus of PIF/DCD amino acid sequence. This segment (from 19-50 residues) is critical for some of its biological activities, including neuron survival. This result is coherent with successive failure of crystallization of the protein. Taken together, these data suggest that the disorder and order transition may be relevant for some biological functions of PIF/DCD.

Prediction and biochemical characterization of intrinsic disorder in the structure of proteolysis-inducing factor/dermcidin

Proteolysis-inducing factor/dermcidin (PIF/DCD) is a novel human gene, located on chromosome 12, locus 12q13.1, that encodes a secreted 110-amino acid protein. Two transcripts for the protein have been identified in normal skin, breast, placenta and brain, and in various primary and metastatic tumor cells. The putative native-state structure of PIF/DCD has not been resolved. Here, we describe some biochemical features of the soluble recombinant 11-kDa protein produced in Escherichia coli. The native 11-kDa polypeptide displayed an anomalous mobility on 1% SDS-PAGE under reduced conditions and appeared as a single ~16-kDa band. Under nonreduced conditions, we detected by mass spectrometry, the presence of multiple peaks corresponding to m/z values of 21 kDa, which we confirmed as a dimeric form with a disulfide bridge between cysteine 34 of each 11-kDa monomer. The native protein exhibited an unusually high susceptibility to proteolytic attack by trypsin, and up to 13 peptides derived from its C-terminus were produced after 5 min of incubation. The secondary structure analysis of PIF/DCD native protein in aqueous solution, by circular dichroism spectroscopy, revealed regions with non-well-defined secondary structure but that acquired á-helix and â-sheet secondary structures in the presence of TFE/water mixtures and micellar and non-micellar SDS molecules. By using PONDR®, DisEMBL™, DisProt, and GlobPlot™ computational predictors, we identified a long disorder region at the N-terminus of PIF/DCD amino acid sequence. This segment (from 19-50 residues) is critical for some of its biological activities, including neuron survival. This result is coherent with successive failure of crystallization of the protein. Taken together, these data suggest that the disorder and order transition may be relevant for some biological functions of PIF/DCD.

Expression and prognostic significance of Cathepsin L in early cutaneous malignant melanoma.

Cathepsins are papain-like lysosome cysteine proteases involved in tumor growth, invasiveness and spread, angiogenesis and alteration in immune and inflammatory responses. We investigated the differences in cathepsin L (CatL) concentrations in primary cutaneous malignant melanoma stage I and normal skin and correlated these values with well-established malignant melanoma prognostic factors. The study was performed on 36 patients (17 men and 19 women; mean age 54 years; range 21-84 years) with histological confirmed primary malignant melanomas less than 1.5 mm thick. The CatL concentrations were measured in 36 pairs of triton extracts of cytosols prepared from the tumor and adjacent normal tissue samples (matched pairs). The CatL concentrations were determined by commercially available enzyme-liked immunosorbent (ELISA) assay from KRKA (Novo Mesto, Slovenia). Significantly higher concentrations of CatL were detected in malignant melanomas than in normal surrounding skin (6.73 vs. 1.42 ng/mg total protein (mgp), p<0.001). Significant correlations between malignant melanoma and normal skin concentrations for CatL were found. The malignant melanoma CatL concentrations correlated significantly with normal skin (r=0.38; p=0.021). CatL concentrations were significantly lower (p<0.01) in the malignant melanomas of Breslow thickness 0.75 mm, Clark invasion of >or=II and

Induced resistance in the human non small cell lung carcinoma (NCI-H460) cell line in vitro by anticancer drugs.

Exposure of human non-small cell lung cancer cells (NCI-H460) to gradually increasing concentrations of doxorubicin resulted in the appearance of a new cell line (NCI-H460/R) that was resistant to doxorubicin (96.2-fold) and cross-resistant to etoposide, paclitaxel, vinblastine and epirubicin. Slight cross-resistance to two MDR-unrelated drugs 8-Cl-cAMP and sulfinosine was observed. Flow cytometry analysis showed that the accumulation of doxorubicin in the resistant cells was 88.4% lower than in the parental cells. Also, verapamil significantly decreased the efflux rate in NCI-H460 and NCI-H460/R cells, whereas curcumin inhibited the efflux in NCI-H460 cells only. Gene expression data confirmed the induction of mdr1 (P-gp), as judged by the observed 15-fold increase in its mRNA concentration in doxorubicin-resistant NCI-H460/R cells. In contrast, mrp1 and lrp expression was unaffected by the doxorubicin resistance. Further work should develop a rationale for a novel treatment of NSCLC with appropriate modulators of resistance aimed at improving the outcome of the acquired drug resistance.